tbuckley/cabot-search huggingface dataset:
Role of drug catabolism, modulation of oncogenic signaling and tumor microenvironment in microbe-mediated pancreatic cancer chemoresistance
Authors: Mjriam Capula, Macarena Perán, Geng Xu, Valentina Donati, Dicky Yee, Alessandro Gregori, Yehuda G. Assaraf, Elisa Giovannetti, Dongmei Deng
Journal: Drug Resistance Updates (2022)

Pancreatic ductal adenocarcinoma (PDAC) has one of the highest incidence/death ratios among all neoplasms due to its late diagnosis and dominant chemoresistance. Most PDAC patients present with an advanced disease characterized by a multifactorial, inherent and acquired resistance to current anticancer treatments. This remarkable chemoresistance has been ascribed to several PDAC features including the genetic landscape, metabolic alterations, and a heterogeneous tumor microenvironment that is characterized by dense fibrosis, and a cellular contexture including functionally distinct subclasses of cancer-associated fibroblasts, immune suppressive cells, but also a number of bacteria, shaping a specific tumor microbiome microenvironment. Thus, recent studies prompted the emergence of a new research avenue, by describing the role of the microbiome in gemcitabine resistance, while next-generation-sequencing analyses identified a specific microbiome in different tumors, including PDAC. Functionally, the contribution of these microbes to PDAC chemoresistance is only beginning to be explored. Here we provide an overview of the studies demonstrating that bacteria have the capacity to metabolically transform and hence inactivate anticancer drugs, as exemplified by the inhibition of the efficacy of 10 out of 30 chemotherapeutics by Escherichia coli. Moreover, a number of bacteria modulate specific oncogenic pathways, such as Fusobacterium nucleatum, affecting autophagy and apoptosis induction by 5-fluorouracil and oxaliplatin. We hypothesize that improved understanding of how chemoresistance is driven by bacteria could enhance the efficacy of current treatments, and discuss the potential of microbiome modulation and targeted therapeutic approaches as well as the need for more reliable models and biomarkers to translate the findings of preclinical/translational research to the clinical setting, and ultimately overcome PDAC chemoresistance, hence improving clinical outcome.
Collaborating to improve monkeypox diagnostics
Authors: Vijay Shankar Balakrishnan
Journal: The Lancet Microbe (2022)

In July, 2022, WHO declared the 2022 multicounty outbreak of monkeypox a public health emergency of international concern (PHEIC). A month later (Aug 18, 2022), WHO reported a global decline of reported monkeypox cases with Europe seemingly reaching its epidemic peak. First identified in a Danish lab in 1958, monkeypox has been endemic to 12 African countries since the 1970s, particularly central African countries such as the Democratic Republic of the Congo. However, it is not until the ongoing 2022 outbreak that global attention has focused on controlling monkeypox and laboratories worldwide have had to adapt.
Ambulance ramping: canaries in the healthcare coalmine
Authors: None The Lancet Healthy Longevity
Journal: The Lancet Healthy Longevity (2022)

The health-care systems in the UK and Australia, already hit hard by the COVID-19 pandemic, remain overstretched. While some elements of care provision are improving (eg, waiting times for routine surgeries), others remain a source of concern. One of the most pressing issues for both systems is the increasing frequency of so-called ambulance ramping, whereby ambulances are required to queue outside overcrowded emergency departments, forced to wait before handing over patients. While this practice ensures that paramedics continue to be with the patient in event of emergency, this can mean that a single ambulance crew is occupied with just one patient for their entire shift or even longer; in some parts of the UK, waiting times of up to 23 h have been recorded.
Associations between insomnia and pregnancy and perinatal outcomes: Evidence from mendelian randomization and multivariable regression analyses
Authors: Qian Yang, Maria Carolina Borges, Eleanor Sanderson, Maria C. Magnus, Fanny Kilpi, Paul J. Collings, Ana Luiza Soares, Jane West, Per Magnus, John Wright, Siri E. Håberg, Kate Tilling, Deborah A. Lawlor
Journal: PLoS Medicine (2022)

Insomnia is common and associated with adverse pregnancy and perinatal outcomes in observational studies. However, those associations could be vulnerable to residual confounding or reverse causality. Our aim was to estimate the association of insomnia with stillbirth, miscarriage, gestational diabetes (GD), hypertensive disorders of pregnancy (HDP), perinatal depression, preterm birth (PTB), and low/high offspring birthweight (LBW/HBW).
Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study
Authors: Sara Ghorashian, Elad Jacoby, Barbara De Moerloose, Susana Rives, Denise Bonney, Geoff Shenton, Peter Bader, Nicole Bodmer, Agueda Molinos Quintana, Blanca Herrero, Mattia Algeri, Franco Locatelli, Kim Vettenranta, Berta Gonzalez, Andishe Attarbaschi, Stephen Harris, Jean Pierre Bourquin, André Baruchel
Journal: The Lancet Haematology (2022)
The Immunobiology and Pathogenesis of Celiac Disease
Authors: Rasmus Iversen, Ludvig M. Sollid
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Among human leukocyte antigen (HLA)-associated disorders, celiac disease has an immunopathogenesis that is particularly well understood. The condition is characterized by hypersensitivity to cereal gluten proteins, and the disease lesion is localized in the gut. Still, the diagnosis can be made by detection of highly disease-specific autoantibodies to transglutaminase 2 in the blood. We now have mechanistic insights into how the disease-predisposing HLA-DQ molecules, via presentation of posttranslationally modified gluten peptides, are connected to the generation of these autoantibodies. This review presents our current understanding of the immunobiology of this common disorder that is positioned in the border zone between food hypersensitivity and autoimmunity.
Acquired Genomic Alterations on First-Line Chemotherapy With Cetuximab in Advanced Colorectal Cancer: Circulating Tumor DNA Analysis of the CALGB/SWOG-80405 Trial (Alliance)
Authors: Kanwal Raghav, Fang-Shu Ou, Alan P. Venook, Federico Innocenti, Ryan Sun, Heinz-Josef Lenz, Scott Kopetz
Journal: Journal of Clinical Oncology (2022)

JCO
Implementing Monocular Visual-Tactile Sensors for Robust Manipulation
Authors: Rui Li, Bohao Peng
Journal: Cyborg and Bionic Systems (2022)

Tactile sensing is an essential capability for robots performing manipulation tasks. In this paper, we introduce a framework to build a monocular visual-tactile sensor for robotic manipulation tasks. Such a sensor is easy to manufacture with affordable ingredients and materials. Based on a marker-based detection method, the sensor can detect the contact positions on a flat or curved surface. In the case study, we have implemented a visual-tactile sensor design specifically through the framework proposed in this paper. The design is low cost and can be processed in a very short time, making it suitable for use as an exploratory study in the laboratory.
Inhibition of advanced glycation end product formation and serum protein infiltration in bioprosthetic heart valve leaflets: Investigations of anti-glycation agents and anticalcification interactions with ethanol pretreatment
Authors: Andrey Zakharchenko, Christopher A. Rock, Tina E. Thomas, Samuel Keeney, Emily J. Hall, Hajime Takano, Abba M. Krieger, Giovanni Ferrari, Robert J. Levy
Journal: Biomaterials (2022)

Bioprosthetic heart valves (BHV) fabricated from heterograft tissue, such as glutaraldehyde pretreated bovine pericardium (BP), are the most frequently used heart valve replacements. BHV durability is limited by structural valve degeneration (SVD), mechanistically associated with calcification, advanced glycation end products (AGE), and serum protein infiltration. We investigated the hypothesis that anti-AGE agents, Aminoguanidine, Pyridoxamine [PYR], and N-Acetylcysteine could mitigate AGE-serum protein SVD mechanisms in vitro and in vivo, and that these agents could mitigate calcification or demonstrate anti-calcification interactions with BP pretreatment with ethanol. In vitro, each of these agents significantly inhibited AGE-serum protein infiltration in BP. However, in 28-day rat subdermal BP implants only orally administered PYR demonstrated significant inhibition of AGE and serum protein uptake. Furthermore, BP PYR preincubation of BP mitigated AGE-serum protein SVD mechanisms in vitro, and demonstrated mitigation of both AGE-serum protein uptake and reduced calcification in vivo in 28-day rat subdermal BP explants. Inhibition of BP calcification as well as inhibition of AGE-serum protein infiltration was observed in 28-day rat subdermal BP explants pretreated with ethanol followed by PYR preincubation. In conclusion, AGE-serum protein and calcification SVD pathophysiology are significantly mitigated by both PYR oral therapy and PYR and ethanol pretreatment of BP.
Breaking Bad News
Authors: J. T. Ptacek
Journal: JAMA (1996)

<h3>Objective.</h3> —To review the literature on breaking bad news while highlighting its limitations and describing a theoretical model from which the bad news process can be understood and studied. <h3>Data Sources.</h3> —Sources were obtained through the MEDLINE database, using "bad news" as the primary descriptor and limiting the sources to English-language articles published since 1985. <h3>Study Selection and Extraction.</h3> —All articles dealing specifically with bad news were examined. These works included letters, opinions, reviews, and empirical studies. Recommendations from these articles were examined, sorted into discrete categories, and summarized. <h3>Data Synthesis.</h3> —The 13 most consistently mentioned recommendations (eg, delivering the news at the patient's pace, conveying some hope, and giving the news with empathy) were examined. <h3>Conclusion.</h3> —Although much has been written on the topic of breaking bad news, the literature is in need of empirical work. Research should begin with the simple question of whether how the news is conveyed accounts for variance in adjustment before moving to more specific questions about which aspects of conveying bad news are most beneficial. It is suggested that the bad news process can be understood from the transactional approach to stress and coping.
The Click-Murmur Syndrome
Authors: Melvin D. Cheitlin
Journal: JAMA (1981)

AUSCULTATORY sounds of a late systolic murmur, with or without a preceding nonejection click, have been generally recognized since the late 1950s to result from abnormal movement of the mitral valve apparatus during systole. Although the mitral valvular origin of these sounds was suspected before, it was only after left ventricular angiography showed the late systolic murmur to result from mitral insufficiency, which was secondary to the abnormal billowing of the mitral leaflets into the left atrium, that the true nature of these auscultatory findings was recognized. The patient with a nonejection click, with and without a systolic murmur, has been described in the literature under a wide variety of names (Table 1). With the demonstration by echocardiography of the abnormal posterior systolic movement of both aortic and mural leaflets of the mitral valve, it has been possible to identify noninvasively the patients with an abnormally prolapsing mitral valve, even
Talc and Ovarian Cancer
Authors: P. Hartge, R. Hoover, L. P. Lesher, L. McGowan
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Cramer and co-workers<sup>1</sup>recently reported observing an association between talc use and risk of ovarian cancer. We therefore examined data on talc use that two of us (L.M. and L.P.L.) had collected as part of a case-control interview studyof epithelial ovarian cancer conducted from 1974 to 1977 in the Washington, DC, area.<sup>2</sup>The cases were 197 women with pathologically confirmed primary epithelial ovarian cancers treated in participating hospitals. The controls were 197 women treated at the same hospitals for conditions other than gynecologic, psychiatric, or malignant diseases or pregnancy. The controls were frequency matched to the cases on age, race, and hospital. The interviewers asked questions about reproductive and sexual history, medical history, drug use, and other exposures. Questions about talc use were added to the questionnaire after the study began, so 135 cases and 171 controls were asked about talc exposure. The reported
Renovascular Occlusive Disease
Authors: John H. Foster
Journal: JAMA (1975)

The blood pressure response to operative treatment in 502 patients with renal artery stenosis and coexisting hypertension was as follows: 51% cured, 15% improved, and 34% failure. The operative mortality was 5.9%. Patients with unilateral fibromuscular disease had a favorable blood pressure response (79.8%) more frequently than the patients with unilateral atherosclerosis (63.4%). In patients with bilateral stenosis, a favorable result occurred in 56%. The anatomic failure rate due to thrombosis of arterial reconstructions, as well as the operative mortality, varied considerably between institutions. If preoperative diagnostic studies demonstrated significant functional disparity between kidneys, and if the operation was anatomically successful, then approximately 80% of these patients were benefited by surgical intervention. (<i>JAMA</i>231:1043-1048, 1975)
Lower Availability of Mitochondrial Complex I in Anterior Cingulate Cortex in Autism: A Positron Emission Tomography Study
Authors: Yasuhiko Kato, Masamichi Yokokura, Toshiki Iwabuchi, Chihiro Murayama, Taeko Harada, Takafumi Goto, Taishi Tamayama, Yosuke Kameno, Tomoyasu Wakuda, Hitoshi Kuwabara, Seico Benner, Atsushi Senju, Hideo Tsukada, Sadahiko Nishizawa, Yasuomi Ouchi, Hidenori Yamasue
Journal: American Journal of Psychiatry (2022)

Mitochondrial dysfunction has been implicated in the pathophysiology of autism spectrum disorder (ASD) in previous studies of postmortem brain or peripheral samples. The authors investigated whether and where mitochondrial dysfunction occurs in the living brains of individuals with ASD and to identify the clinical correlates of detected mitochondrial dysfunction.This case-control study used positron emission tomography (PET) with 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF), a radioligand that binds to the mitochondrial electron transport chain complex I, to examine the topographical distribution of mitochondrial dysfunction in living brains of individuals with ASD. Twenty-three adult males with high-functioning ASD, with no psychiatric comorbidities and free of psychotropic medication, and 24 typically developed males with no psychiatric diagnoses, matched with the ASD group on age, parental socioeconomic background, and IQ, underwent [18F]BCPP-EF PET measurements. Individuals with mitochondrial disease were excluded by clinical evaluation and blood tests for abnormalities in lactate and pyruvate levels.Among the brain regions in which mitochondrial dysfunction has been reported in postmortem studies of autistic brains, participants with ASD had significantly decreased [18F]BCPP-EF availability specifically in the anterior cingulate cortex compared with typically developed participants. The regional specificity was revealed by a significant interaction between diagnosis and brain regions. Moreover, the lower [18F]BCPP-EF availability in the anterior cingulate cortex was significantly correlated with the more severe ASD core symptom of social communication deficits.This study provides direct evidence to link in vivo brain mitochondrial dysfunction with ASD pathophysiology and its communicational deficits. The findings support the possibility that mitochondrial electron transport chain complex I is a novel therapeutic target for ASD core symptoms.
Association Between Polygenic Risk Scores and Outcome of ECT
Authors: Robert Sigström, Kaarina Kowalec, Lina Jonsson, Caitlin C. Clements, Robert Karlsson, Axel Nordenskjöld, Erik Pålsson, Patrick F. Sullivan, Mikael Landén
Journal: American Journal of Psychiatry (2022)

Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.
Charting the Landscape of Genetic Overlap Between Mental Disorders and Related Traits Beyond Genetic Correlation
Authors: Guy Hindley, Oleksandr Frei, Alexey A. Shadrin, Weiqiu Cheng, Kevin S. O’Connell, Romain Icick, Nadine Parker, Shahram Bahrami, Naz Karadag, Daniel Roelfs, Børge Holen, Aihua Lin, Chun C. Fan, Srdjan Djurovic, Anders M. Dale, Olav B. Smeland, Ole A. Andreassen
Journal: American Journal of Psychiatry (2022)

Objective: Mental disorders are heritable and polygenic, and genome-wide genetic correlations (rg) have indicated widespread shared genetic risk across multiple disorders and related traits, mirroring their overlapping clinical characteristics. However, rg may underestimate the shared genetic underpinnings of mental disorders and related traits because it does not differentiate mixtures of concordant and discordant genetic effects from an absence of genetic overlap. Using novel statistical genetics tools, the authors aimed to evaluate the genetic overlap between mental disorders and related traits when accounting for mixed effect directions. Methods: The authors applied the bivariate causal mixture model (MiXeR) to summary statistics for four mental disorders, four related mental traits, and height from genome-wide association studies (Ns ranged from 53,293 to 766,345). MiXeR estimated the number of “causal” variants for a given trait (“polygenicity”), the number of variants shared between traits, and the genetic correlation of shared variants (rgs). Local rg was investigated using LAVA. Results: Among mental disorders, ADHD was the least polygenic (5.6K “causal” variants), followed by bipolar disorder (8.6K), schizophrenia (9.6K), and depression (14.5K). Most variants were shared across mental disorders (4.4K–9.3K) and between mental disorders and related traits (5.2K–12.8K), but with disorder-specific variations in rg and rgs. Overlap with height was small (0.7K–1.1K). MiXeR estimates correlated with LAVA local rg (r=0.88, p<0.001). Conclusions: There is extensive genetic overlap across mental disorders and related traits, with mixed effect directions and few disorder-specific variants. This suggests that genetic risk for mental disorders is predominantly differentiated by divergent effect distributions of pleiotropic genetic variants rather than disorder-specific variants. This represents a conceptual advance in our understanding of the landscape of shared genetic architecture across mental disorders, which may inform genetic discovery, biological characterization, nosology, and genetic prediction.
Disentangling the cognitive, physical, and mental health sequelae of COVID-19
Authors: Conor J. Wild, Loretta Norton, David K. Menon, David A. Ripsman, Richard H. Swartz, Adrian M. Owen
Journal: Cell Reports Medicine (2022)

As COVID-19 cases exceed hundreds of millions globally, many survivors face cognitive challenges and prolonged symptoms. However, important questions about the cognitive effects of COVID-19 remain unresolved. In this cross-sectional online study, 478 adult volunteers who self-reported a positive test for COVID-19 (mean = 30 days since most recent test) perform significantly worse than pre-pandemic norms on cognitive measures of processing speed, reasoning, verbal, and overall performance, but not short-term memory, suggesting domain-specific deficits. Cognitive differences are even observed in participants who did not require hospitalization. Factor analysis of health- and COVID-related questionnaires reveals two clusters of symptoms-one that varies mostly with physical symptoms and illness severity, and one with mental health. Cognitive performance is positively correlated with the global measure encompassing physical symptoms, but not the one that broadly describes mental health, suggesting that the subjective experience of "long COVID" relates to physical symptoms and cognitive deficits, especially executive dysfunction.
Everyone’s going to make a mistake, but how can we make things better?
Authors: Anthea Martin
Journal: BMJ (2022)

Everyone's going to make a mistake, but how can we make things better? Anthea Martin medicolegal consultantEveryone will make a mistake at some point in their medical career.Some of these mistakes will be minor with little impact on the patient or clinician, others will be more significant and may cause real harm, resulting in consequences not only for the patient, but for the doctor too.